1. Technical Field
The invention relates to polypeptides. More particularly, the invention relates to gp100-derived polypeptides that contain both a helper T-cell epitope and a cytotoxic T-cell epitope.
2. Background Information
For some time many groups have been actively identifying cytotoxic T lymphocyte (CTL) epitopes for various tumor-associated antigens (TAA) and synthetic polypeptides representing these epitopes have been used to prepare therapeutic vaccines to treat cancer patients (Marchand M P et al., Int J of Cancer 63:883 (1995); Jager E et al., Int J of Cancer 67:54 (1996); Weber J et al., J Immunother 22:431 (1999); Rosenberg S A et al., Nat Med 4:321 (1998); and Zaks T Z et al., Cancer Res 58:4902 (1998)). However, therapeutic effects of these vaccines are far from optimal.
Several TAA are possible targets for developing T-cell immunotherapy against malignant melanoma (Boon, T et al., J Exp Med 183:725 (1996) and Wang R F et al., Immunol Rev 170:85 (1999)). Amongst these, the melanocyte-related antigen gp100 is currently being evaluated in the clinic (Rosenberg S A et al., Nat Med 4:321 (1998) and Kawakami Y et al., J Immunol 154:3961 (1995)). Numerous CTL epitopes restricted by the MHC class I alleles HLA-A2, -A3, -A11, -A24 and Cw8 have been reported (Kawakami Y et al., J Immunol 154:3961 (1995); Cox A L et al., Science 264:716 (1994); Tsai V. et al., J Immunol 158:1796 (1997); Kawashima I et al., 1998. Int J Cancer 78:518 (1998); Skipper J C et al., J Immunol 157:5027 (1996); Kawakami Y et al., J Immunol 161:6985 (1998); Robbins P F et al, J Immunol 159:303 (1997); and Castelli C et al, J Immunol 162:1739 (1999)). On the other hand, only one HTL epitope, which is restricted by the HLA-DR*0401 MHC class II allele, expressed in approximately one fourth of the population, has been described (Li K, et al., Cancer Immunol Immunother 47:32 (1998) and Touloukian C E et al., J Immunol 164:3535 (2000)).